Figure 6.

ADSL is a candidate for selection in the modern human lineage, after the split from Neanderthal and Denisova. (A) One of the top-scoring regions when running 3P-CLR (0.25-cM windows) on the modern human lineage contains genes TNRC6B, ADSL, MKL1, MCHR1, SGSM3, and GRAP2. The most disruptive nonsynonymous modern-human-specific change in the entire list of top regions is in an exon of ADSL and is fixed derived in all present-day humans but ancestral in archaic humans. It is highly conserved across tetrapods and lies only three residues away from the most common mutation leading to severe adenylosuccinase deficiency. (B) The ADSL gene codes for a tetrameric protein. The mutation is in the C-terminal domain of each of the tetrameric units (red arrows), which are near the active sites (light blue arrows). Scores in A were standardized using the chromosome-wide mean and standard deviation. Vertebrate alignments were obtained from the UCSC genome browser (Vertebrate Multiz Alignment and Conservation track) and the image was built using the GenomeGraphs package in Bioconductor and Cn3D.